Polymorphisms in the Hypoxia Inducible Factor 1-α and the Impact on the Prognosis of Early Stages of Oral Cancer
Polymorphisms in the Hypoxia Inducible Factor 1-α and the Impact on the Prognosis of Early Stages of Oral Cancer
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DOI：
10.1245/s10434-009-0503-8
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发表时间：
2009-08-01
影响因子：
3.7
通讯作者：
Gamallo, Carlos
中科院分区：
文献类型：
--
作者：
Fernando Munoz-Guerra, Mario;Encarnacion Fernandez-Contreras, Maria;Gamallo, Carlos
缺氧诱导因子 1 (HIF-1) 是细胞对缺氧反应的关键调节因子，可能在肿瘤生长的控制中发挥着核心作用。最近已鉴定出在常氧条件下增加其体外活性和稳定性的多态性或突变。在本研究中，我们旨在探讨位于 HIF-1 α 外显子 12 内的 C1772T 和 G1790A 单核苷酸多态性 (SNP) 对早期口腔鳞状细胞癌 (OSCC) 预后的影响。通过 PCR-RFLP 测定了 139 个健康人 DNA 样本中 C1772T 和 G1790A 多态性的频率。 志愿者和 74 名接受手术治疗的 T1/2 N0 OSCC 患者。研究了 HIF-1 α SNP 对肿瘤大小、浸润深度、病理特征和组织学分级的影响。通过 Kaplan-Meier 分析和时序检验评估基因型与复发和/或疾病特异性生存之间的相关性。关于 G1790A SNP，患者中 GA 杂合子和 AA 变异纯合子基因型的频率显着高于健康志愿者（分别为 32.8% vs. 6.5% 和 4.7% vs. 无）（P < .0001）。此外，变异等位基因 A 的存在与疾病复发 (P = .02) 和较短的无病生存期 (P = .04) 相关。 C1772T 的基因型分布在患者和健康受试者之间没有差异，并且在无病生存或总生存方面没有观察到差异。我们的结果表明，HIF-1 α 基因中的 G1790A 多态性可能会导致 OSCC 的易感性，并且可能是早期不良预后的标志。
Hypoxia-inducible factor-1 (HIF-1) is the key regulator of cellular responses to hypoxia and presumably plays a central role in the control of tumor growth. Polymorphisms or mutations increasing its activity and stability in vitro under normoxia have recently been identified. In this study, we aimed to investigate the effect of C1772T and G1790A single nucleotide polymorphisms (SNPs), located within the exon 12 of HIF-1 alpha on the prognosis of early stages of oral squamous cell carcinoma (OSCC).The frequency of C1772T and G1790A polymorphisms was determined by PCR-RFLP in 139 DNA samples from healthy volunteers and 74 patients with surgically treated T1/2 N0 OSCC. The impact of HIF-1 alpha SNPs on tumor size, invasive depth, pathological features, and histological grade was studied. Correlations between genotype and relapse and/or disease-specific survival were evaluated by Kaplan-Meier analysis and log-rank test.Concerning G1790A SNP, the frequencies of GA heterozygous and AA variant homozygous genotypes were significantly higher in patients than in healthy volunteers (32.8% vs. 6.5% and 4.7% vs. none, respectively) (P < .0001). Also, the presence of the variant allele A was associated to disease-relapse (P = .02) and shorter disease-free survival (P = .04). The genotype distribution of C1772T did not diverge between patients and healthy subjects, and no differences were observed with respect to disease-free or overall survival.Our results suggest that G1790A polymorphism in the HIF-1 alpha gene might confer susceptibility to OSCC and could be a marker of disfavorable prognosis at early stages.